Limosilactobacillus reuteri DSM 17938 relieves inflammation, endoplasmic reticulum stress, and autophagy in hippocampus of western diet-fed rats by modulation of systemic inflammation.

The consumption of western diets, high in fats and sugars, is a crucial contributor to brain molecular alterations, cognitive dysfunction and neurodegenerative diseases. Therefore, a mandatory challenge is the individuation of strategies capable of preventing diet-induced impairment of brain physiology. A promising strategy might consist in the administration of probiotics that are known to influence brain function via the gut-brain axis. In this study, we explored whether Limosilactobacillus reuteri DSM 17938 (L. reuteri)-based approach can counteract diet-induced neuroinflammation, endoplasmic reticulum stress (ERS), and autophagy in hippocampus, an area involved in learning and memory, in rat fed a high fat and fructose diet. The western diet induced a microbiota reshaping, but L. reuteri neither modulated this change, nor the plasma levels of short-chain fatty acids. Interestingly, pro-inflammatory signaling pathway activation (increased NFkB phosphorylation, raised amounts of toll-like receptor-4, tumor necrosis factor-alpha, interleukin-6, GFAP, and Haptoglobin), as well as activation of ERS (increased PERK and eif2α phosphorylation, higher C/EBP-homologous protein amounts) and autophagy (increased beclin, P62-sequestosome-1, and LC3 II) was revealed in hippocampus of western diet fed rats. All these hippocampal alterations were prevented by L. reuteri administration, showing for the first time a neuroprotective role of this specific probiotic strain, mainly attributable to its ability to regulate western diet-induced metabolic endotoxemia and systemic inflammation, as decreased levels of lipopolysaccharide, plasma cytokines, and adipokines were also found. Therapeutic strategies based on the use of L. reuteri DSM17938 could be beneficial in reversing metabolic syndrome-mediated brain dysfunction and cognitive decline.

Age-Dependent Skeletal Muscle Mitochondrial Response to Short-Term Increased Dietary Fructose.

The harmful effect of a long-term high-fructose diet is well established, but the age-dependent physiological responses that can be triggered by a short-term high-fructose diet in skeletal muscles have not been deeply explored. Therefore, the aim of this work was to compare the alterations in mitochondrial energetic and insulin responsiveness in the skeletal muscle induced by a short-term (2 weeks) fructose feeding in rats of different ages. For this purpose, fructose and uric acid levels, insulin sensitivity, mitochondrial bioenergetics and oxidative status were evaluated in the skeletal muscles from young (30 days old) and adult (90 days old) rats. We showed that, even in the short term, a high-fructose diet has a strong impact on skeletal muscle metabolism, with more marked effects in young rats than in adults ones. In fact, despite both groups showing a decrease in insulin sensitivity, the marked mitochondrial dysfunction was found only in the young rats, thus leading to an increase in the mitochondrial production of ROS, and therefore, in oxidative damage. These findings underscore the need to reduce fructose consumption, especially in young people, to preserve the maintenance of a metabolically healthy status.

Limosilactobacillus reuteri DSM 17938 reverses gut metabolic dysfunction induced by Western diet in adult rats.

Introduction: Microencapsulation of probiotic bacteria is an efficient and innovative new technique aimed at preserving bacterial survival in the hostile conditions of the gastrointestinal tract. However, understanding whether a microcapsule preserves the effectiveness of the bacterium contained within it is of fundamental importance. Methods: Male Wistar rats aged 90 days were fed a control diet or a Western diet for 8 weeks, with rats fed the Western diet divided into three groups: one receiving the diet only (W), the second group receiving the Western diet and free L. reuteri DSM 17938 (WR), and the third group receiving the Western diet and microencapsulated L. reuteri DSM 17938 (WRM). After 8 weeks of treatment, gut microbiota composition was evaluated, together with occludin, one of the tight junction proteins, in the ileum and the colon. Markers of inflammation were also quantified in the portal plasma, ileum, and colon, as well as markers for gut redox homeostasis. Results: The Western diet negatively influenced the intestinal microbiota, with no significant effect caused by supplementation with free and microencapsulated L. reuteri. However, L. reuteri, in both forms, effectively preserved the integrity of the intestinal barrier, thus protecting enterocytes from the development of inflammation and oxidative stress. Conclusion: From these whole data, it emerges that L. reuteri DSM 17938 can be an effective probiotic in preventing the unhealthy consequences of the Western diet, especially in the gut, and that microencapsulation preserves the probiotic effects, thus opening the formulation of new preparations to be able to improve gut function independent of dietary habits.